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Trial record 1 of 1 for:    CPI-0610, Acute Leukemia, Myelodysplastic Syndrome, Myelodysplastic/ Myeloproliferative Neoplasms, and Myelofibrosis
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A Phase 2 Study of CPI-0610 With and Without Ruxolitinib in Patients With Myelofibrosis

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ClinicalTrials.gov Identifier: NCT02158858
Recruitment Status : Recruiting
First Posted : June 9, 2014
Last Update Posted : August 20, 2018
Sponsor:
Collaborator:
The Leukemia and Lymphoma Society
Information provided by (Responsible Party):
Constellation Pharmaceuticals

Brief Summary:

Phase 1 Part (Complete): Open-label, sequential dose escalation study of CPI-0610 in patients with previously treated Acute Leukemia, Myelodysplastic Syndrome, Myelodysplastic/Myeloproliferative Neoplasms, and Myelofibrosis.

Phase 2 Part: Open-label study of CPI-0610 with and without Ruxolitinib in patients with Myelofibrosis.

CPI-0610 is a small molecule inhibitor of bromodomain and extra-terminal (BET) proteins.


Condition or disease Intervention/treatment Phase
Leukemia, Myelocytic, Acute Myelodysplastic Syndrome (MDS) Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable Myelofibrosis Drug: CPI-0610 Drug: Ruxolitinib Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 114 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2 Study of CPI-0610, a Small Molecule Inhibitor of BET Proteins: Phase 1 (Dose Escalation of CPI-0610 in Patients With Hematological Malignancies) and Phase 2 (Dose Expansion of CPI- 0610 With and Without Ruxolitinib in Patients With Myelofibrosis)
Study Start Date : June 2014
Estimated Primary Completion Date : April 2019
Estimated Study Completion Date : March 2020


Arm Intervention/treatment
Experimental: CPI-0610 Monotherapy
In the Phase 2 portion, patients with Myelofibrosis who have failed JAK inhibitor therapy will be assigned to the monotherapy arm (CPI-0610 alone).
Drug: CPI-0610
Experimental: Combination
Patients with Myelofibrosis who are on a stable dose of a JAK inhibitor will be assigned to the combination therapy arm (CPI-0610 + Ruxolitinib)
Drug: CPI-0610
Drug: Ruxolitinib



Primary Outcome Measures :
  1. Phase 2 Part: Evaluate spleen response [ Time Frame: By imaging after 24 weeks ]
  2. Phase 2 Part: Evaluate the RBC transfusion independence rate [ Time Frame: Absence of RBC transfusion and no hemoglobin level below 8 g/dL in the prior 12 weeks ]

Secondary Outcome Measures :
  1. Phase 2 Part: Evaluate the duration of spleen response [ Time Frame: By palpation and imaging after 24 weeks ]
  2. Phase 2 Part: Evaluate response rate [ Time Frame: Rate of response by IWG-MRT after 24 weeks ]
  3. Phase 2 Part: Evaluate the change in patient reported outcomes [ Time Frame: Chnages from baseline in the total symptom score (MFSAF v4.0) and PGIC ]
  4. Phase 2 Part: Evaluate the rate of RBC transfusion and the RBC transfusion dependence rate [ Time Frame: Average number of RBC units per subject-month ]
  5. Phase 2 Part: Pharmacokinetic parameters of CPI-0610 and ruxolitinib: AUC [ Time Frame: Assessed during cycle 1 (first 21 days on study) ]
  6. Phase 2 Part: Pharmacokinetic parameters of CPI-0610 and ruxolitinib: Cmax [ Time Frame: Assessed during cycle 1 (first 21 days on study) ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adult (aged ≥ 18 years)
  • Phase 2 Part: Patients with confirmed diagnosis of MF who meet all of the following criteria: (a) DIPSS of intermediate-1 or higher, (b) Platelet count: ≥ 75 (monotherapy arm) or ≥ 100 (combination arm), (c) ANC ≥ 1.0, (d) Palpable spleen ≥ 5cm, (e) Peripheral blood blast count <10%, (f) At least 2 symptoms measurable using the MFSAF v4.0, (g) Monotherapy Arm patients: Previously treated with a JAK inhibitor and be intolerant, resistant, refractory or lost response to the JAK inhibitor, (h) Combination Arm patients: Be on a stable dose of Ruxolitinib
  • ECOG performance status ≤2.
  • Adequate hematological, renal, hepatic, and coagulation laboratory assessments
  • Patients must give written informed consent to participate in this study before the performance of any study-related procedure.

Exclusion Criteria:

  • Phase 2 Part: Patients who have had prior splenectomy or have had splenic irradiation within 3 months of starting study drug
  • Current infection with HIV, Hepatitis B or Hepatitis C
  • Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of CPI-0610, including any unresolved nausea, vomiting, or diarrhea that is CTCAE grade >1
  • Impaired cardiac function or clinically significant cardiac diseases
  • Uncontrolled cardiac arrhythmia (patients with rate-controlled atrial fibrillation are not excluded.)
  • Any other concurrent severe and/or uncontrolled concomitant medical condition that could compromise participation in the study (e.g., clinically significant pulmonary disease, clinically significant neurological disorder, active or uncontrolled infection)
  • Systemic anti-cancer treatment with a small molecule therapeutic (other than Ruxolitinib for the Combination arm) other than hydroxyurea less than 2 weeks before the first dose of CPI-0610
  • Administration of a therapeutic antibody less than 4 weeks before the first dose of CPI-0610. A minimum 2-week period between the last treatment with a therapeutic antibody and the first dose of CPI-0610 may be permitted in patients with rapidly progressive disease, following discussion with the medical monitor
  • Treatment with an investigational small molecule less than 2 weeks before the first dose of CPI-0610. In addition, the first dose of CPI-0610 should not occur before a period equal to or greater than 5 half-lives of the small molecule investigational agent has elapsed
  • Treatment with medications that are known to be strong inhibitors or inducers of CYP450 enzymes
  • Treatment with medications that are known to carry a risk of Torsades de Pointes
  • Immunosuppressive treatment that cannot be discontinued both prior to study entry and for the duration of the study. Oral prednisone at a dose of 10 mg or less per day is allowed, as are other oral corticosteroids given at glucocorticoid-equivalent doses. Topical, nasal and inhaled corticosteroids are also allowed
  • Pregnant or lactating women
  • Women of child-bearing potential and men with reproductive potential, if they are unwilling to use adequate contraception while on study therapy and for 3 months thereafter
  • Patients unwilling or unable to comply with the study protocol

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02158858


Contacts
Contact: Debbie Johnson 617-714-0555 debbie.johnson@constellationpharma.com

Locations
United States, California
UCLA Medical Center Recruiting
Los Angeles, California, United States, 90095
Contact: Farzam Hariri       FHariri@mednet.ucla.edu   
Principal Investigator: Gary Schiller, MD         
United States, Indiana
Horizon Oncology Center Recruiting
Lafayette, Indiana, United States, 47905
Contact: Wael Harb, MD    765-446-5111    info@horizonbioadvance.com   
Principal Investigator: Wael Harb, MD         
United States, Massachusetts
Massachusetts General Hospital Active, not recruiting
Boston, Massachusetts, United States, 02114
United States, New York
Icahn School of Medicine at Mount Sinai Recruiting
New York, New York, United States, 10029
Contact: Frank Fabris    212-241-8999    frank.fabris@mssm.edu   
Principal Investigator: Marina Kremyanskya, MD PhD         
Memorial Sloan-Kettering Cancer Center Active, not recruiting
New York, New York, United States, 10065
United States, Ohio
Gabrail Cancer Center Recruiting
Canton, Ohio, United States, 44718
Contact: Carrie Smith, RN       CSmith@GabrailCancerCenter.com   
Principal Investigator: Nashat Gabrail, MD         
United States, Pennsylvania
University of Pennsylvania - Perelman Center for Advanced Medicine Active, not recruiting
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Kurt Schroeder, RN    713-563-2622    kdschroe@mdanderson.org   
Principal Investigator: Prithviraj Bose, MD         
Canada, British Columbia
St. Paul's Hospital Recruiting
Vancouver, British Columbia, Canada, V6Z 2A5
Contact: Rachel Despotovic    604-875-5296    rachel.despotovic@vch.ca   
Principal Investigator: Lynda Foltz, MD         
Sponsors and Collaborators
Constellation Pharmaceuticals
The Leukemia and Lymphoma Society
Investigators
Study Director: Debbie Johnson Constellation Pharmaceuticals

Responsible Party: Constellation Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02158858     History of Changes
Other Study ID Numbers: 0610-02
First Posted: June 9, 2014    Key Record Dates
Last Update Posted: August 20, 2018
Last Verified: August 2018

Keywords provided by Constellation Pharmaceuticals:
Phase 1/2
Oncology
BET Inhibitor
Ruxolitinib

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Preleukemia
Primary Myelofibrosis
Myeloproliferative Disorders
Myelodysplastic-Myeloproliferative Diseases
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms
Leukemia
Neoplasms by Histologic Type
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions